As one of the nation's leading academic research centers, the University of Pittsburgh has both an opportunity and an obligation to take the inherent risks associated with reengineering a successful research enterprise to undertake a transformative initiative that will result in the development and advancement of clinical and translational science as a distinct discipline in western Pennsylvania. The University is committed to transforming its culture, environment, and structure to achieve this goal by forming the Clinical and Translational Science Institute (CTSI). The CTSI will serve as the integrative academic home for clinical and translational scientists across the University's six health sciences schools;Carnegie Mellon University;the University of Pittsburgh Medical Center (UPMC), one of the nation's largest and most financially successful academic health care systems;and the region. The CTSI's primary focus is to develop, nurture, and support a cadre of clinical and translational scientists by building on the University's existing clinical research training programs (Roadmap K12, K30) to establish a comprehensive program with activities ranging from early research exposure for high school students to advanced doctoral programs. Through "integration and innovation," the CTSI will excel in the development of new biomedical knowledge and the translation of that knowledge from the basic and preclinical research settings to individuals, communities, and health practice. The Children's Hospital of Pittsburgh's General Clinical Research Center (GCRC) and the four sites of the University of Pittsburgh GCRC will be reengineered, integrated, and augmented by new CTSI communitybased and minority health focused centers to develop efficient, accessible, and widely used participant and clinical interaction resources. The CTSI Center for Clinical and Translational Informatics, which is developing translational research informatics tools for the NCI Cancer Biomedical Informatics Grid Initiative, will infuse informatics tools into the entire lifecycle of clinical research studies and develop an online collaborative research community. Innovative interdisciplinary research initiatives will be developed through the ten CTSI resource cores and translated to health practice via a novel CTSI community partnership program and through centralization of UPMC's extensive clinical networks. The resulting transformations in the institution, scientist, research, and health practice will improve health locally, regionally, and nationally.